Worldwide, 12 million people acquire syphilis every year, and many are co-infected with HIV. Evidence suggests that HIV-infected people are more likely than HIV-uninfected people to develop symptomatic neurosyphilis. The burden of syphilis and HIV falls most heavily on the developing world where the resources to diagnose neurosyphilis are lacking. In the US, a combination of the CSF-VDRL (cerebrospinal fluid Venereal Disease Research Laboratory) test and laboratory-based CSF treponemal tests are used to evaluate the possibility of neurosyphilis. The CSF-VDRL test is specific for the diagnosis of neurosyphilis, but is not sensitive. In contrast, the CSF treponemal tests are sensitive, but not specific. In the developing world, these 2 tests are not available or are performed only at distant laboratories. Thus there is very limited opportunity to establish the diagnosis of symptomatic neurosyphilis and such cases are often missed. Simple and rapid tests for use on CSF would facilitate the diagnosis of neurosyphilis in local settings throughout the world. The rapid plasma reagin (RPR) test is widely available in the developing world and is used on serum to establish a syphilis diagnosis. It is simpler to perform than the VDRL test. However, this test has not been developed for use on CSF. The World Health Organization (WHO) recently evaluated 6 commercial rapid, treponemal tests on serum that are inexpensive and simple to perform. 4 of them were recommended for field trials. Our preliminary studies suggest that the rapid treponemal tests or the RPR test on CSF may be specific for diagnosis of neurosyphilis. The goal of this application is to develop point-of-care CSF tests to , rapidly and simply diagnose symptomatic neurosyphilis in resource poor settings. It takes advantage of an ongoing study of neurosyphilis in the US. The specific aims are: 1) Determine the sensitivity and specificity of the 4 WHO-evaluated rapid treponemal tests on CSF for diagnosis of neurosyphilis and identify the best test for use in Aims 3 and 4; 2) Optimize the RPR for use on CSF and determine its sensitivity and specificity for diagnosis of neurosyphilis; 3) Determine the time to normalization of the CSF treponemal test (chosen in Aim 1) and of the CSF-RPR after neurosyphilis treatment; 4) Determine the ability of the best treponemal test identified in Aim 1 and of the CSF-RPR to diagnose neurosyphilis in real time in a US outpatient clinic. The results of this study will be used to design field trials in the areas of greatest need.